What Clinicians Should Know About Tonmya’s FDA Approval

Relief on the Horizon: FDA Approves Fibromyalgia Treatment
What Has Been Approved: Tonmya (TNX-102 SL)
On August 15, 2025, the U.S. Food and Drug Administration (FDA) approved Tonmya, a sublingual formulation of cyclobenzaprine hydrochloride (cyclobenzaprine HCl), for the treatment of fibromyalgia in adults. This marks the first new FDA-approved therapy for fibromyalgia in over 15 years. WebMD+5Pharmacy Times+5Medscape+5

Tonmya is made by Tonix Pharmaceuticals and is also known by its investigational name TNX-102 SL. It is designed as a once-daily bedtime sublingual tablet (under the tongue) aimed at improving sleep quality and reducing pain. Because of its sublingual route, it has faster absorption and avoids first-pass hepatic metabolism. This also reduces production of norcyclobenzaprine, a long half-life metabolite implicated in side effects of standard oral cyclobenzaprine. AFSA+3The Rheumatologist+3Neurology Advisor+3

Clinical Trial Evidence: What Supports the Approval
Two large Phase III trials provided the principal evidence for approval: the RELIEF and RESILIENT trials. These measured pain reduction, symptom relief, sleep improvements, and overall function.

RELIEF Trial (NCT04172831)

• Enrolled ~503 adult fibromyalgia patients. AJMC+1
  
  
• Treatment arm: Tonmya (TNX-102 SL) given at bedtime. Comparator: placebo.
  
  
• Outcomes: Patients on Tonmya had a greater reduction in daily pain from baseline to week 14 than placebo. Improvements were also seen in sleep quality, fatigue, and other fibromyalgia symptom scores. The Rheumatologist+2AJMC+2
  

RESILIENT Trial (NCT05273749)

• Enrolled ~457 patients with fibromyalgia across U.S. sites.
  
  
• Measured change from baseline daily pain severity using numeric rating scales over 14 weeks, plus secondary endpoints: Fibromyalgia Impact Questionnaire-Revised (FIQR), PROMIS sleep disturbance, fatigue, global impression, etc.
  
  
• Results: The Tonmya group showed statistically and clinically significant pain reduction compared to placebo. Also, significant improvements were observed in sleep disturbance and fatigue domains. Side effects were generally mild. The Rheumatologist+2Neurology Advisor+2
  

How Tonmya Works & What Makes It Different
Tonmya is not a completely novel molecule but rather a novel formulation and delivery method. Cyclobenzaprine is an older drug (approved in the 1970s as a skeletal muscle relaxant) that has long been used off-label for symptoms of fibromyalgia, particularly to aid sleep. The Rheumatologist+1

What distinguishes Tonmya:

• Sublingual absorption: Faster systemic uptake, bypassing first-pass metabolism. This minimizes norcyclobenzaprine buildup, which is associated with sedative and other side effects in oral formulations.
  
  
• Once-daily bedtime dosing: Designed to target nonrestorative sleep, which is a central, often neglected component of fibromyalgia pathophysiology. Nonrestorative sleep is thought to perpetuate widespread pain, fatigue, and cognitive dysfunction.
  
  
• Safety/tolerability profile: The most common side effects in trials were oral hypoesthesia (numbness), taste alteration, mild dizziness, and fatigue. Most were transient and mild. The Rheumatologist+1
  

Where Tonmya Fits in the Fibromyalgia Treatment Landscape
Fibromyalgia is a chronic pain syndrome characterized by widespread musculoskeletal pain, fatigue, sleep disturbance, cognitive difficulties (“fibro-fog”), and mood symptoms. Existing FDA-approved medications include:

• Pregabalin (Lyrica)
  
  
• Duloxetine (Cymbalta)
  
  
• Milnacipran (Savella)
  

These treatments have variable efficacy, and many patients continue to have significant pain, poor sleep, or intolerance of side effects. Tonmya adds to these options, especially for patients whose sleep disturbance is a major contributor to their symptom burden. Its approval means clinicians have more flexibility, particularly for those who may not have tolerated or responded adequately to the older medications. AJMC+1

Patient Profiles: Who May Benefit Most
From the data and trial populations, some patient characteristics may predict a better response to Tonmya:

• Adults with diagnosed fibromyalgia (as per ACR criteria or similar) who have significant sleep disturbance or nonrestorative sleep. The Rheumatologist+2Renal & Urology News+2
  
  
• Patients who have had insufficient relief from prior treatments (pregabalin, duloxetine, milnacipran) or who experienced intolerable side effects.
  
  
• Patients who prefer nonopioid treatments consider the risk of dependency and side effect burden.
  

On the other hand, certain patients may need careful consideration, such as those with:

• Significant cardiac conduction issues (cyclobenzaprine has anticholinergic and other receptor activities).
  
  
• Severe hepatic impairment (first-pass metabolism and sublingual absorption may still implicate hepatic pathways).
  
  
• Interactions with other sedatives or medications with anticholinergic burden.
  

Practical Clinical Implementation & Dosing

• Administration: Tonmya is taken once daily at bedtime, under the tongue (sublingually) per the approved label. This timing leverages its sleep-improving properties.

• Dose escalation: In trials, the initial dose was 2.8 mg (one sublingual tablet) during a run-in period, followed by 5.6 mg (two tablets) nightly in subsequent weeks. Monitoring for side effects is necessary. The Rheumatologist
  
  
• Expected Onset: Pain reduction was measurable over 14 weeks in the trials; improvements in sleep and fatigue were also observed. Clinicians should set realistic expectations with patients: this is not instantaneous, but over weeks.
  
  
• Monitoring: Typical side effects include oral numbness or taste disturbances. These are usually mild and resolve. Clinicians should monitor for excessive sedation, interaction with other CNS depressants, or anticholinergic effects.
  
  
• Availability: Commercial availability is expected in Q4 of 2025. Cost and insurance coverage will influence patient access. Tonix affirmed in their announcements that they anticipate availability in the fourth quarter. Tonix Pharmaceuticals Holding Corp.+1
  

Risks, Limitations, and Open Questions
While Tonmya is promising, some caveats remain:

• Effect size: The pain reduction, while statistically significant, is modest when compared to placebo. Not all patients achieve large improvements. Some secondary endpoints (like patient global impression) varied in the RELIEF vs RESILIENT trials. The Rheumatologist+1
  
  
• Real-world effectiveness: Trial populations are selected, and comorbidities may differ in broader practice. Tolerability outside of controlled settings may differ.
  
  
• Side effects: Oral mucosal symptoms (numbness, taste alterations) are relatively common. For patients with underlying tongue or mouth sensitivities, caution is warranted.
  
  
• Long-term safety: Data beyond ~14-week trial durations are limited. Long-term impact on sleep architecture, cognition, or other organ systems remains to be seen.
  
  
• Cost and access issues: As with all new medications, pricing and insurance reimbursement will affect uptake.
  

Implications for Clinical Practice
Integration into Treatment Algorithms
Oncologists, rheumatologists, pain physicians, and primary care providers managing fibromyalgia should consider Tonmya in patients who meet criteria, especially where sleep disturbance is prominent. Treatment guidelines will likely be updated in 2026 to include it as a recommended option.

Shared Decision-Making
Given modest effect sizes and the potential for side effects, patients should be informed about:

• Other existing therapies and their risks/benefits.
  
  
• Lifestyle interventions: exercise, cognitive behavioral therapy for insomnia (CBT-I), and physical therapy.
  
  
• Realistic expectations: improvement vs cure.
  

Potential for Combination Therapy
There may be a benefit in combining Tonmya with existing treatment modalities (e.g., duloxetine, pregabalin) for synergistic effects, particularly when sleep disturbance remains refractory. Clinical trial data for such combinations are not yet published.

Broader Significance: Why This Approval Matters

• First new option in over a decade: Many patients have been frustrated with long periods of limited innovation in fibromyalgia treatment. Tonmya offers renewed hope. The Rheumatologist+1
  
  
• Targeting sleep: Sleep problems in fibromyalgia are central to the disease, not merely associated symptoms. By focused targeting of nonrestorative sleep, Tonmya addresses an often under-managed domain.
  
  
• Nonopioid analgesic: In an era of concern over opioid misuse, a nonopioid option with analgesic properties is particularly valued.
  

Future Directions & Research Needed

1. Long-term safety studies: Necessitated to assess impact over 6-12 months and beyond, especially regarding sleep architecture, cognition, and mood.
   
   
2. Comparative effectiveness research: Direct head-to-head trials vs existing approved agents (pregabalin, duloxetine, milnacipran) to determine relative efficacy and tolerability.
   
   
3. Real-world evidence (RWE): Observational studies in varied populations (comorbid depression, obesity, older patients) to assess generalizability.
   
   
4. Biomarker development: Identifying which phenotypes of fibromyalgia (e.g., those with prominent sleep disturbance, those with neuropathic pain features) respond best to Tonmya.
   
   
5. Cost-effectiveness analysis: Especially important for insurance coverage and payer decisions.
   
   
6. Global approval: Regulatory bodies outside the US (EMA, etc.) will be watching; global availability will depend on further trial data and local regulatory processes.
   

Key Practical Points for Clinicians

• Screen fibromyalgia patients for severity of sleep disturbance—use validated questionnaires (e.g., Pittsburgh Sleep Quality Index) to quantify.
  
  
• When Tonmya becomes available, consider it especially in patients who have had an inadequate response to standard therapies, or who reported sleep problems as accentuating other symptoms.
  
  
• Monitor closely for side effects, including oral cavity discomfort, sedation, and possible interactions with other prescriptions.
  
  
• Adjust expectations: improvements are meaningful, but not a cure; therapy likely needs to be continued nightly to maintain benefit.
  
  
• Monitor patient-reported outcomes (pain, sleep quality, fatigue, function) rather than only objective measures.